Through the use of group-specific chemical modifications, essential active site residues are being identified in contractile proteins including those of sarcoplasmic reticulum membranes. This approach is also being used to determine the accessibility of a given type of side chain, including how this accessibility may change as the protein undergoes transtitions during its functional cycle. The possible proximity of these proteins is being tested with cross-linking agents which can produce stable covalent bonds between neighboring polypeptide chains associated in vivo by non-covalent interactions. Syntheses of ATP analogs are being carried out. These analogs serve to label or probe the type of environment of the active sites. In labeling experiments the aim is to isolate and characterize peptides containing active site residues. Active site probes include ATP analogs to which chromophoric, fluorescent or paramagnetic moieties are attached.